Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease: Case series and review of literature

Abstract

Anti-tumor necrosis factor (TNF) biologics are currently amongst the most widely used and efficacious therapies for inflammatory bowel disease (IBD). The development of therapeutic drug monitoring for infliximab and adalimumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients (75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

Keywords: Inflammatory bowel disease, Adalimumab, Anti-tumor necrosis factor, Infliximab, Therapeutic drug monitoring, Drug antibody, Antidrug antibodies, Dose escalation

Core tip: One of the main challenges of anti-tumor necrosis factor use in inflammatory bowel disease is immunogenicity, or the immune-mediated formation of drug antibodies. Therapeutic drug monitoring allows for measurement of serum drug levels and antidrug antibodies. Previously it was thought that antibody formation was indication to switch to an alternate agent; however, more recent literature, which we review in this article, suggests that a low level of antidrug antibodies can be overcome by dose escalation of the biologic drug and/or addition of an immunomodulator. We describe a small case series of patients in whom this strategy was used, in conjunction with therapeutic drug monitoring, with some success.